Treatable Traits in Asthma: The Importance of Extrapulmonary Traits-GERD, CRSwNP, Atopic Dermatitis, and Depression/Anxiety.

Treatable traits is a personalized medicine approach to the management of airway disease. Assessing traits within the 3 domains of pulmonary, extrapulmonary, and behavioral/lifestyle/risk factor traits, and applying targeted treatments to effectively manage these traits, enables a holistic and personalized approach to care. Asthma is a heterogeneous and complex airway disease that is frequently complicated by several extrapulmonary traits that impact asthma outcomes and predict future outcomes. We propose that the identification of extrapulmonary and behavioral risk factor traits and the implementation of targeted therapy will lead to improved management of people with asthma. Furthermore, many extrapulmonary traits present as "connected comorbidities"; that is, they coexist with asthma, have an impact on asthma, and effective treatment improves both asthma and the comorbidity or the comorbidities may share a similar mechanism. In this review, we explore this concept and look at atopic dermatitis, chronic rhinosinusitis with nasal polyps, gastroesophageal reflux disease, anxiety, and depression as treatable traits of asthma and how these can be managed using this approach.

Treatable traits in asthma during pregnancy: a call for a shift towards a precision-based management approach.

Asthma is the most common chronic medical condition in pregnancy. Asthma exacerbations in pregnancy are unpredictable, and are associated with adverse maternal and fetal perinatal outcomes such as preterm birth and low birthweight. Goals of asthma management in pregnancy are to establish effective asthma control and prevent exacerbations. Optimising the management of asthma in pregnancy is an important goal of practice and future research.Treatable traits is a precision medicine paradigm proposed for the management of airways diseases, which holistically addresses the complexity and heterogeneity of airways disease. It is an individualised treatment approach that aims to improve outcomes. This makes treatable traits well suited for pregnant women with asthma, who have a high prevalence of obesity, mental health conditions, poor symptom perception and suboptimal asthma management skills including low treatment adherence. These traits are measurable and treatable. In this review, we explore current knowledge on the burden of asthma, maternal and perinatal consequences of asthma during pregnancy, the treatable traits paradigm, the prevalence of treatable traits in pregnant women with asthma, and consider how the treatable traits paradigm can be integrated into the management of asthma in pregnancy.

Smartphone app-delivered gut-directed hypnotherapy improves symptoms of self-reported irritable bowel syndrome: A retrospective evaluation.

BACKGROUND: Gut-directed hypnotherapy (GDH) has high rates of durable efficacy for treating irritable bowel syndrome (IBS) but its widespread use is limited due to high costs and poor access. A smartphone app delivering GDH was developed to fill gaps in accessibility but has not been assessed in IBS patients. The current retrospective evaluation aims to assess the efficacy of app-delivered GDH in managing IBS symptoms and to investigate associating factors that predict response. METHODS: Irritable bowel syndrome patients who downloaded the app between June 2019 and April 2020 were retrospectively evaluated. The first seven sessions were free. Daily GDH, psycho-education, and breathing exercises were included. Overall and individual gastrointestinal symptoms were assessed at baseline and completion using a 100-mm visual analogue scale. Clinical data were extracted. KEY RESULTS: 2843 patients with self-reported IBS commenced the free sessions, 1428 (50%) purchased the app and 253 (9%) completed all 42 sessions. Outcome data were available for 190 users who completed all 42 sessions. 64% of patients who completed the GDH and provided outcome data responded (defined as >30% reduction in abdominal pain). Abdominal pain reduced from 60mm (50-73mm) at baseline to 26mm (13-50mm) on study completion (p<0.001 Wilcoxon). Similar results were seen for overall and individual symptoms. On multivariable analysis, symptom response was positively associated with being ≥ 40 years (estimated OR 0.398, p=0.025) and negatively associated with trying probiotics (0.323, p=0.042). CONCLUSIONS & INFERENCES: Adherence to app-delivered gut-directed hypnotherapy was low but users who completed the program saw notable improvements in their IBS symptoms. Patients ≥40 years, with symptoms for ≥5 years, may respond better. A controlled trial comparing face-to-face to app-delivered GDH is indicated.

T2-low: what do we know?: Past, present, and future of biologic therapies in noneosinophilic asthma.

T2-low asthma is an often severe asthma subtype with limited treatment options and biologic therapeutics are lacking. Several monoclonal antibodies (mAbs) targeting non-T2 cytokines were previously reported to be ineffective in asthma. These trials often investigated heterogeneous asthma populations and negative outcomes could be related to unsuitable study cohorts. More tailored approaches in selecting participants based on specific biomarkers have been beneficial in treating severe T2-high asthma. Similarly, mAbs previously deemed ineffective bear the potential to be useful when administered to the correct target population. Here, we review individual clinical trials conducted between 2005 and 2021 and assess the suitability of the selected cohorts, whether study end points were met, and whether outcome measures were appropriate to investigate the effectiveness of the respective drug. We discuss potential target groups within the T2-low asthma population and suggest biomarkers that may predict a treatment response. Furthermore, we assess whether biomarker-guided approaches or subgroup analyses were associated with more positive study outcomes. The mAbs directed against alarmins intervene early in the inflammatory cascade and are the first mAbs found to have efficacy in T2-low asthma. Several randomized controlled trials performed predefined subgroup analyses that included T2-low asthma. Subgroup analyses were associated with positive outcomes and were able to reveal a stronger response in at least 1 subgroup. A better understanding of T2-low subgroups and specific biomarkers is necessary to identify the most responsive target population for a given mAb.

The Role of Food in the Treatment of Bowel Disorders: Focus on Irritable Bowel Syndrome and Functional Constipation.

Irritable bowel syndrome (IBS) and functional constipation (FC) are among the most common disorders of gut-brain interaction, affecting millions of individuals worldwide. Most patients with disorders of gut-brain interaction perceive food as a trigger for their gastrointestinal symptoms, and specific dietary manipulations/advice have now been recognized as a cornerstone therapeutic option for IBS and FC. We discuss in detail the 2 most common dietary interventions used for the management of IBS-general dietary advice based on the National Institute for Health and Care Excellence guidelines and a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). We summarize the literature around the possible mechanisms of FODMAP-mediated IBS pathophysiology, the current 3-step, top-down approach of administering a low FODMAP diet (LFD) (restriction phase, followed by reintroduction and personalization), the efficacy data of its restriction and personalization phases, and possible biomarkers for response to an LFD. We also summarize the limitations and challenges of an LFD along with the alternative approach to administering an LFD (e.g., bottom-up). Finally, we discuss the available efficacy data for fiber, other dietary interventions (e.g., Mediterranean diet, gluten-free diet, and holistic dietary interventions), and functional foods (e.g., kiwifruit, rhubarb, aloe, and prunes) in the management of IBS and FC.

Diet as a therapeutic tool in chronic gastrointestinal disorders: Lessons from the FODMAP journey.

BACKGROUND AND AIM: Diet is a powerful tool in the management of gastrointestinal disorders, but developing diet therapies is fraught with challenge. This review discusses key lessons from the FODMAP diet journey. METHODS: Published literature and clinical experience were reviewed. RESULTS: Key to designing a varied, nutritionally adequate low-FODMAP diet was our accurate and comprehensive database of FODMAP composition, made universally accessible via our user-friendly, digital application. Our discovery that FODMAPs coexist with gluten in cereal products and subsequent gluten/fructan challenge studies in nonceliac gluten-sensitive populations highlighted issues of collinearity in the nutrient composition of food and confirmation bias in the interpretation of dietary studies. Despite numerous challenges in designing, funding, and executing dietary randomized controlled trials, efficacy of the low-FODMAP diet has been repeatedly demonstrated, and confirmed by real-world experience, giving this therapy credibility in the eyes of clinicians and researchers. Furthermore, real-world application of this diet saw the evolution of a safe and effective three-phased approach. Specialist dietitians must deliver this diet to optimize outcomes as they can target and tailor the therapy and to mitigate the key risks of compromising nutritional adequacy and precipitating disordered eating behaviors, skills outside the gastroenterologist's standard tool kit. While concurrent probiotics are ineffective, specific fiber supplements may improve short-term and long-term outcomes. CONCLUSIONS: The FODMAP diet is highly effective, but optimal outcomes are contingent on the involvement of a gastroenterological dietitian who can assess, educate, and monitor patients and manage risks associated with implementation of this restrictive diet.

Accuracy of Gastrointestinal Ultrasound and Calprotectin in the Assessment of Inflammation and its Location in Patients with an Ileoanal Pouch.

BACKGROUND AND AIMS: In symptomatic patients with ileoanal pouches, pouchoscopy is needed for accurate diagnosis but is invasive. We aimed to assess the utility of non-invasive gastrointestinal ultrasound and faecal calprotectin in ileoanal pouch patients. METHODS: Patients with an ileoanal pouch were consecutively enrolled in this cross-sectional study from clinics in Victoria, Australia. The pouchitis disease activity index was used as a reference standard. Video-recorded pouchoscopies were reviewed by three gastroenterologists. Pouch, pre-pouch, and cuff biopsies were reviewed by a single pathologist. Ultrasound was performed by a single gastroenterologist transabdominally and transperineally. Faecal calprotectin was measured from morning stool samples. All examiners were blinded to patients' clinical history. RESULTS: A total of 44 participants had a pouchoscopy, of whom 43 had a faecal calprotectin test and 42 had an ultrasound; 17 had pouchitis, 15 had pre-pouch ileitis, and 16 had cuffitis. Pouch wall thickness of <3 mm was 88% sensitive in excluding pouchitis, and pouch wall thickness of ≥4 mm was 87% specific in diagnosing pouchitis. Transabdominal ultrasound had good utility [area under the curve: 0.78] in diagnosing moderate-severe pre-pouch ileitis. Transperineal ultrasound had good utility for the diagnosis of pouchitis [area under the curve: 0.79]. Faecal calprotectin differentiated inflammatory from non-inflammatory pouch disorders, such as irritable pouch syndrome, with an area under the curve of 0.90. Faecal calprotectin <100 µg/g ruled out inflammatory pouch disorders with a sensitivity of 94%. CONCLUSIONS: Faecal calprotectin and ultrasound are accurate and complementary tests to diagnose and localise inflammation of the ileoanal pouch. Prospective studies are needed to validate proposed sonographic indices and calprotectin levels.

Dietary fibres and IBS: translating functional characteristics to clinical value in the era of personalised medicine.

Clinical guidelines in the use of fibre supplementation for patients with IBS provide one-size-fits-all advice, which has limited value. This narrative review addresses data and concepts around the functional characteristics of fibre and subsequent physiological responses induced in patients with IBS with a view to exploring the application of such knowledge to the precision use of fibre supplements. The key findings are that first, individual fibres elicit highly distinct physiological responses that are associated with their functional characteristics rather than solubility. Second, the current evidence has focused on the use of fibres as a monotherapy for IBS symptoms overall without attempting to exploit these functional characteristics to elicit specific, symptom-targeted effects, or to use fibre types as adjunctive therapies. Personalisation of fibre therapies can therefore target several therapeutic goals. Proposed goals include achieving normalisation of bowel habit, modulation of gut microbiota function towards health and correction of microbial effects of other dietary therapies. To put into perspective, bulking fibres that are minimally fermented can offer utility in modulating indices of bowel habit; slowly fermented fibres may enhance the activities of the gut microbiota; and the combination of both fibres may potentially offer both benefits while optimising the activities of the microbiota throughout the different regions of the colon. In conclusion, understanding the GI responses to specific fibres, particularly in relation to the physiology of the individual, will be the future for personalising fibre therapy for enhancing the personalised management of patients with IBS.

The Patients' Experience of Severe Asthma Add-On Pharmacotherapies: A Qualitative Descriptive Study.

PURPOSE: Add-on therapies for severe asthma are continually emerging with proven efficacy in randomised controlled trials. To date, however, there are no qualitative studies exploring patients' experiences with these treatments. We aimed to understand the experience of patients who were treated with an add-on therapy for their severe asthma. PATIENTS AND METHODS: A qualitative descriptive study was conducted, participants were recruited from the respiratory clinics and databases of a tertiary referral hospital. Participants with treatment-refractory severe asthma (n=20) prescribed an add-on therapy for >4 months (75% mepolizumab; 25% omalizumab, and 25% macrolide) were recruited. Qualitative semi-structured interviews were conducted, with interviews thematically analysed. RESULTS: Participants' mean (SD) age was 59.5 (15.3) years, and 50% were male. Participants reported 4.5 (2.3) exacerbations in the past year. Asthma Control Questionnaire score was 2.0 (1.4). The monoclonal add-on therapies had been prescribed for a median (IQR) of 12.5 (7.0, 24.0) months. Experience was captured in four emergent themes: "Life is just easier" provided an overall message that the add-on therapy made the participants' life easier in terms of increasing participation, levelling out symptoms, providing more energy and reducing healthcare use. "Prednisone: A necessary evil" was discussed, particularly in terms of dose and dependence and damaging side effects. The theme "worry and hope for the future" referenced treatment non-response or cessation of effect which was discussed by some participants. Finally, "holistic care" was centred on the sentiment that the participant's asthma management and overall health were not related to one aspect or medication alone. CONCLUSION: Patients with severe asthma experience vast improvements in quality-of-life and life participation with add-on therapies, but there remains a significant burden related to oral corticosteroids and incomplete treatment responses. Addressing this residual burden is an important area for future research.

A feasibility randomised controlled trial of Novel Activity Management in severe ASthma-Tailored Exercise (NAMASTE): yoga and mindfulness.

BACKGROUND: Physical inactivity is common in severe asthma and associated with poor health outcomes. New approaches are needed to address physical inactivity in this group. OBJECTIVE: To examine whether yoga and mindfulness improves health-related quality of life (HRQoL) compared with a minimal active control group and collect feasibility data to inform future studies. METHODS: Over 12-weeks, adults with severe asthma were recruited. Participants were randomised 2:1 to parallel yoga or control groups. All participants received an activity tracker. The yoga group received tailored group classes twice a week for 16-weeks with a qualified yoga instructor. The control group set activity goals with a research officer and received eight progress calls. Outcomes were assessed at 16-weeks. Primary outcome was St George's Respiratory Questionnaire (SGRQ). Secondary outcomes included asthma control, physical activity, breathlessness, and inflammation. Face-to-face qualitative interviews were conducted to determine acceptability. RESULTS: There were 15 participants randomised to yoga (mean 67 years; 60% female) and 9 to control (68 years; 56% female). Planned comparisons indicated the yoga group had greater SGRQ improvement than the control group. There was little change in secondary outcomes. Moderate-vigorous activity increased substantially in the control group. Participants found the intervention acceptable; key barriers and facilitators were social connection, the setting, addressing breathing and asthma symptoms, changing their mindset, and the intersection of different elements. CONCLUSION: A yoga and mindfulness intervention was feasible, acceptable to patients and improved HRQoL. The findings will inform design of much needed future research into physical activity interventions for severe asthma. World Health Organization International Clinical Trials Registry Platform The study was registered under the Australian New Zealand Clinical Trials Registry (ANZCTR) on the 26th of November 2018, Trial ID ACTRN12618001914257.

Behavioral and Diet Therapies in Integrated Care for Patients With Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is a common, symptom-based condition that has negative effects on quality of life and costs health care systems billions of dollars each year. Until recently, management of IBS has focused on over-the-counter and prescription medications that reduce symptoms in fewer than one-half of patients. Patients have increasingly sought natural solutions for their IBS symptoms. However, behavioral techniques and dietary modifications can be effective in treatment of IBS. Behavioral interventions include gastrointestinal-focused cognitive behavioral therapy and gut-directed hypnotherapy to modify interactions between the gut and the brain. In this pathway, benign sensations from the gut induce maladaptive cognitive or affective processes that amplify symptom perception. Symptoms occur in response to cognitive and affective factors that trigger fear of symptoms or lack of acceptance of disease, or from stressors in the external environment. Among the many dietary interventions used to treat patients with IBS, a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols is the most commonly recommended by health care providers and has the most evidence for efficacy. Patient with IBS who choose to follow a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols should be aware of its 3 phases: restriction, reintroduction, and personalization. Management of IBS should include an integrated care model in which behavioral interventions, dietary modification, and medications are considered as equal partners. This approach offers the greatest likelihood for success in management of patients with IBS.

Delivery of Acetate to the Peripheral Blood after Consumption of Foods High in Short-Chain Fatty Acids.

SCOPE: To promote local and systemic benefits of short-chain fatty acids (SCFA), methods of increasing their delivery to the gastrointestinal tract are needed. SCFA in foods and beverages represents a poorly characterized source. Main aims of this study are: 1) quantify SCFA in commonly consumed foods and beverages, and 2) explore the pharmacokinetics of consuming oral SCFA from dietary sources. METHODS AND RESULTS: Gas-chromatography coupled to flame ionization detection is used measure SCFA in 38 commonly consumed foods and beverages. Acetate is the most abundant SCFA detected, with kombucha and vinegar found to provide >1000 mg of acetate per serve. An acute pharmacokinetic study is conducted in 10 participants. Acetate is stable across the 2-h sampling period after consumption of a control drink, with consumption of a vinegar drink containing 25 mmol acetate significantly increasing plasma acetate concentration after 60 min and increasing acetate delivery to the blood upon assessment of the area under the pharmacokinetic curve. CONCLUSION: Fermented foods and beverages are a natural source of dietary SCFA that acutely deliver SCFA to the blood. If systemic delivery is needed for immunological and metabolic effects to occur, these may be achieved if delivered over a longer period of time.

Review article: FODMAPS, prebiotics and gut health-the FODMAP hypothesis revisited.

BACKGROUND: Restriction of dietary FODMAP intake can alleviate symptoms in patients with irritable bowel syndrome. Because many FODMAPs have prebiotic actions, there is concern that their dietary restriction leads to dysbiosis with health consequences, and their intake is being encouraged by addition to foods and via supplements. AIMS: To examine the hazards and benefits of high and low FODMAP intake. METHODS: Current literature was reviewed and alternative hypotheses formulated. RESULTS: Low FODMAP intake reduces abundance of faecal Bifidobacteria without known adverse outcomes and has no effect on diversity, but the reduction in bacterial density may potentially be beneficial to gut health. Supplementary prebiotics can markedly elevate the intake of FODMAPs over levels consumed in the background diet. While this increases the abundance of Bifidobacteria, it adversely affects gut health in animal studies by inducing colonic mucosal barrier dysfunction, mucosal inflammation and visceral hypersensitivity. Rapid colonic fermentation is central to the identified mechanisms that include injury from high luminal concentrations of short-chain fatty acids and low pH, and inflammatory effects of increased endotoxin load and glycation of macromolecules. Whether these observations translate into humans requires further study. Opposing hypotheses are presented whereby excessive intake of FODMAPs might have health benefits via prebiotic effects, but might also be injurious and contribute to the apparent increase in functional intestinal disorders. CONCLUSIONS: Reduced FODMAP intake has few deleterious effects on gut microbiota. Consequences (both positive and negative) of excessive carbohydrate fermentation in the human intestines from elevated FODMAP intake require more attention.

Randomised clinical trial: transabdominal interferential electrical stimulation vs sham stimulation in women with functional constipation.

BACKGROUND: Managing chronic constipation is challenging as patients frequently remain dissatisfied with laxative treatments. Novel studies using transabdominal electrical interferential therapy in children have shown benefit but there are inadequate adult studies. AIM: To examine the effects of transabdominal interferential stimulation on bowel symptoms and quality of life in women with refractory constipation. METHODS: In a single-blind, randomised, sham-controlled pilot study, women aged ≥18 years with refractory constipation were randomised to receive interferential stimulation (with crossing of electric currents) or a novel sham stimulation (with no crossing of currents) for 1 hour a day for 6 weeks. Primary outcome was the number of patients with ≥3 spontaneous bowel movements/week. Secondary endpoints included change in PAC-SYM (Patient Assessment of Constipation-SYMptoms), PAC-QOL (Patient Assessment of Constipation-Quality of Life) and an overall symptom severity score (measured at baseline, mid time point of stimulation, end of treatment and 3 months after cessation of treatment). RESULTS: Interferential therapy (n = 17) met the primary outcome in 9(53%) compared with 2(12%) with sham therapy (n = 16) (P = 0.02). Interferential therapy resulted in reductions in PAC-SYM (P = 0.03) and overall symptom scores (P = 0.05). Laxative use more than halved in 66% with interferential therapy compared with 14% with sham therapy (P = 0.01). Significant improvements in symptom outcomes were maintained at 3 months. There were no treatment-related adverse effects. CONCLUSION: Transabdominal interferential electrical stimulation is effective in reducing constipation in adult women. Three months after therapy, response is maintained and quality of life improved. Not allowing currents to cross intra-abdominally was an effective placebo. (Australianclinicaltrials.gov.au ACTRN12614000736640).

Fractional exhaled nitric oxide-based asthma management: The feasibility of its implementation into antenatal care in New South Wales, Australia.

BACKGROUND: The use of fractional exhaled nitric oxide (FeNO)-based asthma management during pregnancy can significantly reduce asthma exacerbations in non-smoking pregnant women. The feasibility of implementing this strategy into antenatal care has not been explored. AIMS: To examine the feasibility of implementing FeNO-based asthma management into antenatal clinics in New South Wales (NSW) Australia. MATERIALS AND METHODS: Semi-structured face-to-face interviews with video elicitation were conducted with healthcare professionals (HCPs) providing antenatal care in one of two hospital-based antenatal clinics in NSW, Australia. The video shown demonstrated the use of the FeNO instrument and other aspects of the management strategy, in antenatal care. Interviews were recorded, transcribed and analysed using qualitative content analysis. RESULTS: A total of 20 interviews were conducted with 15 midwives, four obstetricians, and one general practitioner. Two main themes and ten sub-themes arose: Getting a number (sub-themes: engaging, technically easy, objective, predictive, reassuring); and Resourcing (sub-themes: time and timing, systems, staff, education and cost). Comments included: 'It's easy, fast and effective' and 'the main barrier is time'. All HCPs felt capable of facilitating the FeNO-based management strategy, with appropriate education, and were willing to undertake this strategy, saying: '…it would be perfectly acceptable for a midwife or doctor to do it'; also, 'they don't necessarily need to see a physician, it's something that midwives would take on generally…'. CONCLUSION: Participants in this study considered FeNO-based asthma management for pregnant women to be a feasible addition to antenatal care following appropriate provision of resources and education.

Soluble fibre supplementation with and without a probiotic in adults with asthma: A 7-day randomised, double blind, three way cross-over trial.

BACKGROUND: Soluble fibre modulates airway inflammation in animal models. The aim of this study was to investigate the effects of soluble fibre supplementation, with and without a probiotic, on plasma short chain fatty acids (SCFA), airway inflammation, asthma control and gut microbiome in adults with asthma. METHODS: A randomised, double-blinded, placebo controlled 3-way cross-over trial in 17 subjects with stable asthma at the Hunter Medical Research Institute, Newcastle, Australia. Subjects received 3 × 7 day oral interventions in random order; soluble fibre (inulin 12 g/day), soluble fibre + probiotic (inulin 12 g/day + multi-strain probiotic >25 billion CFU) and placebo. Plasma SCFA, sputum cell counts and inflammatory gene expression, asthma control gut microbiota, adverse events including gastrointestinal symptoms were measured. FINDINGS: There was no difference in change in total plasma SCFA levels (µmol/L) in the placebo versus soluble fibre (Δmedian [95% CI] 16·3 [-16·9, 49·5], p = 0·335) or soluble fibre+probiotic (18·7 [-14·5, 51·9], p = 0·325) group. Following the soluble fibre intervention there was an improvement in the asthma control questionnaire (ACQ6) (∆median (IQR) -0·35 (-0·5, -0·13), p = 0·006), sputum %eosinophils decreased (-1.0 (-2·5, 0), p = 0·006) and sputum histone deacetylase 9 (HDAC9) gene expression decreased (-0.49 (-0.83, -0.27) 2-ΔCt, p = .008). Individual bacterial operational taxonomic units changed following both inulin and inulin+probiotic arms. INTERPRETATION: Soluble fibre supplementation for 7 days in adults with asthma did not change SCFA levels. Within group analysis showed improvements in airway inflammation, asthma control and gut microbiome composition following inulin supplementation and these changes warrant further investigation, in order to evaluate the potential of soluble fibre as a non-pharmacological addition to asthma management. FUND: John Hunter Hospital Charitable Trust.

Treatable traits: a new paradigm for 21st century management of chronic airway diseases: Treatable Traits Down Under International Workshop report.

"Treatable traits" have been proposed as a new paradigm for the management of airway diseases, particularly complex disease, which aims to apply personalised medicine to each individual to improve outcomes. Moving new treatment approaches from concepts to practice is challenging, but necessary. In an effort to accelerate progress in research and practice relating to the treatable traits approach, the Treatable Traits Down Under International Workshop was convened in Melbourne, Australia in May 2018. Here, we report the key concepts and research questions that emerged in discussions during the meeting. We propose a programme of research that involves gaining international consensus on candidate traits, recognising the prevalence of traits, and identifying a potential hierarchy of traits based on their clinical impact and responsiveness to treatment. We also reflect on research methods and designs that can generate new knowledge related to efficacy of the treatable traits approach and consider multidisciplinary models of care that may aid its implementation into practice.

AGA Clinical Practice Update on Functional Gastrointestinal Symptoms in Patients With Inflammatory Bowel Disease: Expert Review.

DESCRIPTION: The purpose of this clinical practice update review is to describe key principles in the diagnosis and management of functional gastrointestinal (GI) symptoms in patients with inflammatory bowel disease (IBD). METHODS: The evidence and best practices summarized in this manuscript are based on relevant scientific publications, systematic reviews, and expert opinion where applicable. Best practice advice 1: A stepwise approach to rule-out ongoing inflammatory activity should be followed in IBD patients with persistent GI symptoms (measurement of fecal calprotectin, endoscopy with biopsy, cross-sectional imaging). Best practice advice 2: In those patients with indeterminate fecal calprotectin levels and mild symptoms, clinicians may consider serial calprotectin monitoring to facilitate anticipatory management. Best practice advice 3: Anatomic abnormalities or structural complications should be considered in patients with obstructive symptoms including abdominal distention, pain, nausea and vomiting, obstipation or constipation. Best practice advice 4: Alternative pathophysiologic mechanisms should be considered and evaluated (small intestinal bacterial overgrowth, bile acid diarrhea, carbohydrate intolerance, chronic pancreatitis) based on predominant symptom patterns. Best practice advice 5: A low FODMAP diet may be offered for management of functional GI symptoms in IBD with careful attention to nutritional adequacy. Best practice advice 6: Psychological therapies (cognitive behavioural therapy, hypnotherapy, mindfulness therapy) should be considered in IBD patients with functional symptoms. Best practice advice 7: Osmotic and stimulant laxative should be offered to IBD patients with chronic constipation. Best practice advice 8: Hypomotility agents or bile-acid sequestrants may be used for chronic diarrhea in quiescent IBD. Best practice advice 9: Antispasmodics, neuropathic-directed agents, and anti-depressants should be used for functional pain in IBD while use of opiates should be avoided. Best practice advice 10: Probiotics may be considered for treatment of functional symptoms in IBD. Best practice advice 11: Pelvic floor therapy should be offered to IBD patients with evidence of an underlying defecatory disorder. Best practice advice 12: Until further evidence is available, fecal microbiota transplant should not be offered for treatment of functional GI symptoms in IBD. Best practice advice 13: Physical exercise should be encourage in IBD patients with functional GI symptoms. Best practice advice 14: Until further evidence is available, complementary and alternative therapies should not be routinely offered for functional symptoms in IBD. This Clinical Practice Update was produced by the AGA Institute.

Vedolizumab as Induction and Maintenance for Inflammatory Bowel Disease: 12-month Effectiveness and Safety.

Background: Vedolizumab is approved for moderate to severe Crohn's disease (CD) and ulcerative colitis (UC). We present prospective, 1-year data of the real-world effectiveness and safety of vedolizumab in inflammatory bowel disease. Methods: Consecutive patients receiving vedolizumab for treatment of UC or CD with at least 14 weeks of follow-up, regardless of outcome, were included. Patients had clinical activity scores (Harvey-Bradshaw Index [HBI] or Simple Clinical Colitis Activity Index [SCCAI]) and inflammatory markers prospectively measured at baseline and weeks 14, 30, and 52. Clinical response was defined as a reduction ≥3 in HBI or SCCAI, clinical remission as HBI ≤4 or SCCAI ≤2, steroid-free remission as clinical remission without the need for corticosteroids, and mucosal healing (assessed at 6 months) as a Mayo endoscopic subscore of 0 or 1 or CD-SES <3. Results: A total of 132 patients were included: 61 (45%) male, 94 (71%) with CD, 42 (29%) with UC; 22% and 34% of CD and UC patients, respectively, achieved steroid-free remission by week 14. This increased to 31% in CD patients and plateaued at 35% in UC patients at 12 months. Increasing remission rates to 6 months were seen in patients with CD, but minimal improvements after 3 months of therapy occurred in those with UC. Mucosal healing was achieved in 52% of UC and 30% of CD patients. Most adverse events were minor; 74% remained on vedolizumab at 12 months. Conclusions: In this real-world study, vedolizumab demonstrated similar efficacy and safety seen in pivotal trials, with sustained clinical response in the majority of patients. Similar rates of response were seen in UC and CD patients. 10.1093/ibd/izx067_video1izx067_Video5754037470001.